5-(3-Hydroxymethyl-3-methyl-1-triazeno imidazole-4-carboxamide is a metabolite of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC, DTIC NSC-45388)

Kolar, G.F.; Maurer, Michael; Wildschutte, Michael

doi:10.1016/0304-3835(80)90076-2

Cited by 41 publications

(11 citation statements)

References 9 publications

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“…Cytochrome P450-catalyzed N -demethylation of dacarbazine initiates the release of methyl diazonium, which in turn methylates the O 6 of guanine in DNA (Figure 3) [33,34]. The prodrug formulation makes possible the cellular delivery of a highly reactive chemical agent.…”

Section: Anticancer Prodrug Activationmentioning

confidence: 99%

Cytochrome P450-Activated Prodrugs

Montellano

2013

Future Med. Chem.

129

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A prodrug is a compound that has negligible, or lower, activity against a specified pharmacological target than one of its major metabolites. Prodrugs can be used to improve drug delivery or pharmacokinetics, to decrease toxicity, or to target the drug to specific cells or tissues. Ester and phosphate hydrolysis are widely used in prodrug design because of their simplicity, but such approaches are relatively ineffective for targeting drugs to specific sites. The activation of prodrugs by the cytochrome P450 system provides a highly versatile approach to prodrug design that is particularly adaptable for targeting drug activation to the liver, to tumors or to hypoxic tissues.

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Section: Anticancer Prodrug Activationmentioning

confidence: 99%

Cytochrome P450-Activated Prodrugs

Montellano

2013

Future Med. Chem.

129

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“…Kolar et al have reported (8,9) that hydroxymethyltriazenes may be prepared by reaction of the monomethyltriazene (Ar.N=N-NH-Me) with formaldehyde, but have not elaborated on the general application of the method, which may be a useful entry to hydroxymethyltriazenes not accessible by the route described here (such as those with electron-donating groups in the aryl moiety). Accordingly, a sample of the I-p-cyanophenyl-3-methyltriazene was prepared (10) and was found to react in suspension in aqueous formaldehyde at 0°C very readily to afford an excellent yield of I-p-cyanophenyl-3-hydroxymethyl-3-methyltriazene (1 X = CN, R = Me), which was identical with a sample prepared by Method A.…”

Section: Discussionmentioning

confidence: 99%

Open-chain nitrogen compounds. Part V. Hydroxymethyltriazenes: synthesis of some new alkyl homologues of the anti-tumour 3-methyl-3-hydroxymethyltriazenes and preparation of the derived acetoxymethyl-, benzoyloxymethyl-, and methoxymethyltriazenes

Hemens¹,

Manning²,

Vaughan³

et al. 1984

Can. J. Chem.

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TANG. Can. J . Chcm. 62, 741 (1984).The synthesis of somc ncw I-aryl-3-alkyl-3-hydroxymcthyltriazcncs is dcscribcd. Thc mcthod of coupling a diazonium salt with an alkylamine/formaldchyde mixture has been cxtcndcd to (a) somc diazonium ions withl~trrtr substituents other than -M groups, (b) those with substituents in thc nrthn position. and (c) to homologous alkylamincs (c.g. cthylamine, propylaminc, ctc.). Hydroxymethyltriazencs can also bc prcparcd by the rcaction of a I-aryl-3-mcthyltriazene with formaldchydc. Scvcral new derivatives of thc hydroxymcthyl function havc bccn prcparcd. Rcaction with acctic anhydridc or bcnzoyl chloride in pyridine affords respcctivcly the acctoxymcthyl-ant1 benzoyloxymcthyl-trinzcncs; thc acctatcs and bcnzoatcs rcact rcadily with methanol to give the novel mcthoxymethyltriazcncs. This is the first rcport of a scrics of dialkyltriazcncs with an ether linkagc in the a position. An ether of this type has also bccn obtaincd directly from thc diazonium tluoroboratc salt by coupling with a mixturc of benzylamine and formaldchydc in cthanolic solution.

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“…These compounds suffer metabolic oxidation by cytochrome P450 enzymes to give hydroxymethyltriazenes 3, which, by loss of formaldehyde, generate the cytotoxic monomethyltriazenes 4 ( Figure 1) [7][8][9]. These are known alkylating agents, capable of methylating DNA and RNA [10,11].…”

Section: Figure 1 Herementioning

confidence: 99%